Pharmacokinetics of Ertapenem in Continuous Venovenous Hemodialysis

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00877370
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 24.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Critically ill patients in the intensive care unit often receive continuous hemodialysis to treat their kidney failure. Ertapenem is an antibiotic often used in these patients. Continuous dialysis may remove ertapenem, putting patients at risk for inappropriate treatment of their infection. This study will determine how much ertapenem is removed by continuous hemodialysis.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Failure	Drug: ertapenem	Phase 4

Detailed Description

Subjects receiving CVVHD will receive a one gram dose of ertapenem. Serial blood samples over 24 hours will be taken to assess the ertapenem blood concentrations over time. Spent dialysate and urine samples (if any) will also be measured for ertapenem content to determine how much drug is removed by CVVHD and kidneys. A pharmacokinetic evaluation will be made to determine what is the most appropriate dose for this drug in patients receiving CVVHD to achieve pharmacokinetic and pharmacodynamic goals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Pharmacokinetics of Invanz® (Ertapenem) in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ertapenem subjects will receive ertapenem while receiving CVVHD

Drug: ertapenem; One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.; Other Names: Invanz

Outcome Measures

Primary Outcome Measures

1. Ertapenem Transmembrane Clearance by Continuous Hemodialysis. [24 hours after receiving first 1 gram dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hospitalized in ICU

• Receiving Continuous hemodialysis

• Prescribed ertapenem

• Informed consent granted

Exclusion Criteria:

• < 18 years of age

• Allergy to ertapenem or other carbapenem antibiotic

• Severe, life-threatening reaction to penicillin or cephalosporins

• Patients experiencing or with history of CNS disorders (eg: seizure, stroke)

• Patients experiencing CNS infection

• Inability to complete 24 hours of CVVHD

• Concurrent use of other extracorporeal therapies such as extracorporeal membrane oxygenation, plasmapheresis or intermittent hemodialysis

• Inability to obtain informed consent

• Pregnant and/or breastfeeding women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan University Hospital	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Bruce A Mueller, Pharm.D., University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bruce A. Mueller, Professor of Pharmacy, University of Michigan
• ClinicalTrials.gov Identifier: NCT00877370
• Other Study ID Numbers: HUM00022460
• First Posted: Apr 7, 2009
• Last Update Posted: Sep 28, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Bruce A. Mueller, Professor of Pharmacy, University of Michigan: ertapenem; continuous hemodialysis; pharmacokinetics
• Additional relevant MeSH terms: Renal Insufficiency; Acute Kidney Injury; Ertapenem

Study Results

Participant Flow

Recruitment Details	Subjects were consented and enrolled between April 2009 and March 2011. All subjects were patients receiving care in an intensive care unit at University of Michigan Health System.
Pre-assignment Detail	All patients that qualified for the study were approached. All subjects that gave their consent were enrolled.

Arm/Group Title	Ertapenem
Arm/Group Description	Subjects will receive ertapenem while receiving CVVHD ertapenem : One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ertapenem
Arm/Group Description	Subjects will receive ertapenem while receiving CVVHD ertapenem : One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 50%
>=65 years	4 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (16)
Sex: Female, Male (Count of Participants)
Female	5 62.5%
Male	3 37.5%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Ertapenem Transmembrane Clearance by Continuous Hemodialysis.
Time Frame	24 hours after receiving first 1 gram dose

Outcome Measure Data

Analysis Population Description

All participants were included in the analysis.

Arm/Group Title	Ertapenem
Arm/Group Description	Subjects will receive ertapenem while receiving CVVHD ertapenem : One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.
Measure Participants	8
Mean (Standard Deviation) [mL/min]	10.4 (4.2)

Adverse Events

Arm/Group Title	Ertapenem
Arm/Group Description	Subjects will receive ertapenem while receiving CVVHD ertapenem : One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.
All Cause Mortality
	Ertapenem
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ertapenem
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Ertapenem
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.